通督活血汤治疗腰椎管狭窄症的网络药理学和分子对接机制研究

Mechanism of Tongdu Huoxue Decoction in treatment of lumbar spinal stenosis by network pharmacology and molecular docking

目的运用网络药理学和分子对接探讨通督活血汤治疗腰椎管狭窄症(LSS)的作用机制。方法通过TCMSP、ETCM数据库及文献筛选出通督活血汤活性成分;利用Swiss Target Prediction和Genecards数据库预测活性成分作用靶点及LSS疾病靶点。通过STRING数据库构建潜在作用靶点的蛋白相互作用(PPI)网络并通过Cytoscape 3.8.0软件筛选潜在靶点。通过DAVID工具进行潜在靶点的GO和KEGG富集分析。利用Discovery Studio 2016软件进行分子对接验证。结果通督活血汤核心活性成分为熊竹素、(3R)-去-O-甲基毛狄泼老素、12-甲基十四烷酸和苏木查尔酮;治疗LSS的核心靶点为肿瘤坏死因子(TNF)、基质金属蛋白酶-9(MMP-9)、白细胞介素(IL)-6、IL-1β和AKT1。关键作用通路为TNF信号通路、FoxO信号通路、甲状腺激素信号通路等。核心活性成分与核心作用靶点具有稳定的结合性能。结论本研究初步揭示了通督活血汤的核心活性成分及其多成分、多靶点、多通路治疗LSS的作用机制,为通督活血汤的临床开发提供了依据。

Objective To investigate the mechanism of Tongdu Huoxue Decoction in treatment of lumbar spinal stenosis(LSS)by using network pharmacology and molecular docking.Methods The active components of Tongdu Huoxue Decoction were screened by TCMSP Database,ETCM Database and related literatures;Swiss target prediction and genecards database were used to predict the action targets of active ingredients and disease targets related to LSS.The protein interaction(PPI)network of potential targets was constructed through STRING Database;the key targets were screened through Cytoscape 3.8.0Software.GO and KEGG enrichment analysis of potential targets was carried out by DAVID tool.Finally,molecular docking was carried out by using Discovery Studio 2016 Software.Results Kumatakenin,(3R)-de-O-methyllasiodiplodin,12-Methyltetradecanoic acid and Sappanchalcone were the core active components of Tongdu Huoxue Decoction;tumor necrosis factor(TNF),matrix metalloproteinase(MMP)-9,interluekin(IL)-6,IL-1βand AKT1 were the core targets for the treatment of LSS.The key pathways were TNF signaling pathway,FoxO signaling pathway,thyroid hormone signaling pathway.The core active components and core target had stable binding properties.Conclusion This study reveals the core active components of Tongdu Huoxue Decoction and its mechanism of multi-component,multi-target and multi-channel treatment of LSS,which provides a basis for the clinical development of it.